Cis-5-(N-methylcarbamyl)-1-benzylpyrrolidine-2-carboxylic acid → 8-Benzyl-3-methyl-3,8-diazabicyclo[3.2.1]octane-2,4-dione

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Reaction Steps

Cis-5-(N-methylcarbamyl)-1-benzylpyrrolidine-2-carboxylic acid (32.3 g, 0.123 mole) and acetic anhydride (160 ml) were heated together at 100°C for 45 minutes after all of the solid had dissolved. Removal of solvent in vacuo left a red-brown oil that was dissolved in a minimum amount of benzene. After removal of 2.0 g of unreacted cis-5-(N-methylcarbamyl)-1-benzylpyrrolidine-2-carboxylic acid by filtration, the solution of desired product was chromatographed on 900 g alumina with benzene elution to give 13.2 g (44%) of pure, oily 8-benzyl-3-methyl-3,8-diazabicyclo[3.2.1]octane-2,4-dione. Treatment of a sample with excess ethanolic hydrogen chloride in diethyl ether solution produced a hydrochloride salt, melting point 140°-170°C. A sample of the free base, melting point 73°-75°C, was subsequently obtained by slow crystallization from benzene.

Provenance & Evidence